Search results for "Mediators"
showing 10 items of 245 documents
Polymorphisms of pro-inflammatory genes and prostate cancer risk: a pharmacogenomic approach.
2009
In this paper, we consider the role of the genetics of inflammation in the pathophysiology of prostate cancer (PCa). This paper is not an extensive review of the literature, rather it is an expert opinion based on data from authors' laboratories on age-related diseases and inflammation. The aim is the detection of a risk profile that potentially allows both the early identification of individuals at risk for disease and the possible discovery of potential targets for medication. In fact, a major goal of clinical research is to improve early detection of age-related diseases, cancer included, by developing tools to move diagnosis backward in disease temporal course, i.e., before the clinical…
Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing
2021
AbstractMotoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motor impairments in part by restoring sonic hedgehog signaling and …
A Pilot Study on Prostate Cancer Risk and Pro-Inflammatory Genotypes: Pathophysiology and Therapeutic Implications
2010
Host genetic factors are crucial risk determinants for many human cancers. In this framework, an interesting model is represented by prostate cancer (PC), which is featured by a complex pathophysiology with a strong genetic component. Multiple genes seem to influence PC risk and several single nucleotide polymorphisms (SNPs) of candidate genes modifying PC susceptibility have been identified. It is noteworthy the potential association of common SNPs in pro-inflammatory genes with PC risk, since chronic inflammation is assumed to play a key role in prostate carcinogenesis. With the aim to identify candidate genes as an experimental basis to develop new strategies for both prevention and trea…
Control of Cell Migration and Inflammatory Mediators Production by CORM-2 in Osteoarthritic Synoviocytes
2011
Background Osteoarthritis (OA) is the most widespread degenerative joint disease. Inflamed synovial cells contribute to the release of inflammatory and catabolic mediators during OA leading to destruction of articular tissues. We have shown previously that CO-releasing molecules exert anti-inflammatory effects in animal models and OA chondrocytes. We have studied the ability of CORM-2 to modify the migration of human OA synoviocytes and the production of chemokines and other mediators sustaining inflammatory and catabolic processes in the OA joint. Methodology/Principal Findings OA synoviocytes were stimulated with interleukin(IL)-1β in the absence or presence of CORM-2. Migration assay was…
Trans- but not cis-resveratrol impairs angiotensin-II-mediated vascular inflammation through inhibition of NF-κB activation and peroxisome proliferat…
2010
Abstract Angiotensin II (Ang-II) displays inflammatory activity and is implicated in several cardiovascular disorders. This study evaluates the effect of cis- and trans (t)-resveratrol (RESV) in two in vivo models of vascular inflammation and identifies the cardioprotective mechanisms that underlie them. In vivo, Ang-II–induced arteriolar leukocyte adhesion was inhibited by 71% by t-RESV (2.1 mg/kg, i.v.), but was not affected by cis-RESV. Because estrogens influence the rennin-angiotensin system, chronic treatment with t-RESV (15 mg/kg/day, orally) inhibited ovariectomy-induced arteriolar leukocyte adhesion by 81%, partly through a reduction of cell adhesion molecule (CAM) expression and c…
Toll-like receptor 5 deficiency exacerbates cardiac injury and inflammation induced by myocardial ischaemia-reperfusion in the mouse
2015
Myocardial ischaemia-reperfusion (MIR) triggers a sterile inflammatory response important for myocardial healing, but which may also contribute to adverse ventricular remodelling. Such inflammation is initiated by molecular danger signals released by damaged myocardium, which induce innate immune responses by activating toll-like receptors (TLRs). Detrimental roles have been recently reported for TLR2, TLR3 and TLR4. The role of other TLRs is unknown. We therefore evaluated the role of TLR5, expressed at high level in the heart, in the development of myocardial damage and inflammation acutely triggered by MIR. TLR5−/− and wild-type (WT) mice were exposed to MIR (30 min ischaemia, 2 h reperf…
Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk.
2008
We investigated the effect of atorvastatin monotherapy and combined treatment with atorvastatin and pioglitazone on intima-media thickness, vascular function and the cardiovascular risk profile. In all, 148 patients (76 male, 72 female; aged 61.4±6.5 years; body mass index [BMI] 29.2±4.1 kg/m2; mean±SD) with increased cardiovascular (CV) risk factors were randomised. Intima-media thickness (IMT), the augmentation index (Aix@75), the microvascular response to acetylcholine (LDF), lipid status, and plasma levels of intact proinsulin, adiponectin, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), sCD40L, P-selectin, tissue plasminogen activator …
Neuroprotective effect of Fn14 deficiency is associated with induction of the granulocyte-colony stimulating factor (G-CSF) pathway in experimental s…
2010
Using a transgenic mouse model of ischemic stroke we checked for a possible interaction of antiphospholipid antibodies (aPL) which often cause thromboses as well as central nervous system (CNS) involvement under non-thrombotic conditions and the TWEAK/Fn14 pathway known to be adversely involved in inflammatory and ischemic brain disease. After 7 days, infarct volumes were reduced in Fn14 deficient mice and were further decreased by aPL treatment. This was associated with strongest increase of the endogenous neuroprotective G-CSF/G-CSF receptor system. This unexpected beneficial action of aPL is an example for a non-thrombogenic action and the double-edged nature of aPL.
Gender-Related Immune-Inflammatory Factors, Age-Related Diseases, and Longevity
2010
This review discusses the role of estrogens as pro- or antiinflammatory players in immune-inflammatory responses. In particular, their role in Alzheimer’s disease (AD), an example of immune-inflammatory disease, is discussed briefly. AD is a progressive neurodegenerative disease, which in Western societies accounts for the majority of cases of clinical senile dementia. However, sexual dimorphism of diseases may also depend on factors independent of sex hormones (i.e., a gender effect), as demonstrated by our data on differential longevity in females and males. In fact, differences in mortality between men and women are not only a question of sex that refers to biological differences, but ra…
Severe hypovitaminosis D correlates with increased inflammatory markers in HIV infected patients
2013
Abstract Background Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients. Methods A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone…